New programme of chemotherapy for IDH mutant glioma

Alex Shimura Yamashita, of Johns Hopkins University School of Medicine in Baltimore, USA, and others studied DNA demethylation drugs -- 5-nitrogen heterotlysine (5-Aza), which effectively slowed the growth of idh mutant tumor cell lines, and 5-Aza and TMZ combined to significantly extend the survival of tumor miceThe findings were published online in The Journal of Neuro-Oncology in September 2018- Excerpted from the article chapter(Ref: Yamashita AS, et alNeuro Oncol2018 Sep 3doi: 10.1093/neuonc/noy146TheWHO II-III grade glioma and glioblastoma have isocitric acid dehydrogenase (Idh) gene mutationsThe diffuse growth of glioma is multiple due to the mutation of IDH1 or IDH2, which produces a pathological product - D-2-hydroxyglutarate (D-2-hydroxyglutarate, 2-HG)2-HG can interfere with the cellular metabolic response, leading to the high methylation of the genome (Figure 1), causing gene expression to lose normal epigenetic regulation, thereby initiating the tumor occurrence processTherefore, the reversal of the idh mutation caused by genomic methylation may reduce the degree of tumor malignancyAlex Shimura Yamashita, of Johns Hopkins University School of Medicine in Baltimore, USA, and others studied DNA demethylation drugs -- 5-nitrogen heterotlysine (5-Aza), which effectively slowed the growth of idh mutant tumor cell lines, and 5-Aza and TMZ combined to significantly extend the survival of tumor miceThe findings were published online in The Journal of Neuro-Oncology in September 2018Figure 1The function of IDH when a cell is in a steady state and the abnormal changes caused by the IDH mutation, especially in the area of cell metabolism2HG, D-2-hydroxyl diacid; alpha KG, alpha-ketone diacid; IDH, isocitric acid dehydrogenase; IDHm, IDH mutant researchers evaluated the therapeutic effect soutcomes of 5-Aza using human IDH1 wild and IDH1R132H glioma cell lines and foreign grafts (PDX) derived from patients Cell growth, protein and gene expression, chromatin immunoprecipitation and nucleosome position of glioma cell line treated by 5-Aza were determined to reduce cell growth rate and increase the expression of glioblastic fibromyalin protein (GFAP) The chromatin immunoprecipitation and nucleosome position determination showed that the mechanism of inducing GFAP expression was related to histone modification and the nuclear small body repositioning of GFAP promoters, respectively To evaluate the anti-tumor activity of the drug in the body, 5-Aza can extend the survival of the idh1R132H mutant group of melanoma mice when 5-Aza is used alone in a pneucossphon animal model established by PDX from patients with the IDH1R132H mutation, but this phenomenon was not found in the IDH132H mutant group In addition, 5-Aza improved the therapeutic effect of TMZ in the subcutaneous and in situ PDX model of glioma in the idh1R132H mutant group of mice finally, the authors point out that 5-Aza combined with the TMZ application can extend the survival of animal models that carry THE IDH mutation tumor 5-Aza has been approved by the FDA for use, so the study opens up new avenues for the treatment of gliomas that carry IDH mutation.